The broad goals of this project are to (1) examine the genetic and environmental factors that influence the timing of substance use initiation and explain the link between early first use and later problems; (2) evaluate sibling effects as a source of familial influence on initiation and progression toward problems; and (3) integrate findings regarding alcohol involvement with those for other substances of abuse. My long-term career objective is to develop a program of research that informs prevention and intervention strategies by identifying genetic and environmental risk factors for different stages of alcohol and other substance involvement. Specific Aims There are two primary research aims of this proposal. The first aim will employ measures of alcohol, tobacco, and cannabis use to examine both substance-specific and common sources of risk for early age of initiation and the progression to heavier use and problems. Sources of risk will be evaluated at both the latent genetic and environmental levels and the measured genetic level. The second aim will evaluate the effect of sibling social influence on alcohol, tobacco, and cannabis involvement with regard to both the timing of substance use initiation and the progression from initiation to heavier use and problems. Analyses will be conducted in two datasets: (1) a sample of twins and siblings of varying genetic relatedness assessed in four waves from ages 12-32; and (2) a national community-based sample of adult twin pairs and their siblings aged 24-40. During the period of award, I will obtain training via coursework, attendance at didactic workshops, and meetings with expert consultants in advanced statistical methods for behavior genetic, molecular genetic, and longitudinal data analysis, and will increase my knowledge base of the development and progression of tobacco and cannabis involvement. I will also aim to become proficient in skills necessary for effective manuscript- and grant-writing. These training opportunities will be essential both for the goals of the current project and for my long-term goal of becoming a professor at a research-intensive university. Significance Results from this project could inform theoretical and developmental models of alcohol and other substance involvement, as well as family-based intervention efforts. Integrating findings for alcohol with those for other substances of abuse and clarifying both substance-specific and common risk factors for initiation and progression will indicate which intervention strategies are likely to have the most widespread effects. In addition, findings will help determine whether and how to target sibling influences on substance use, which have been largely ignored in prevention models focused on parent and peer factors.